This study will evaluate the safety and tolerability of eltrombopag in the treatment of low platelet counts in adult subjects with advanced myelodysplastic syndrome (MDS), secondary acute myeloid leukemia after MDS (sAML/MDS), or de novo AML that are relapsed, refractory or ineligible to receive azacitidine, decitabine, intensive chemotherapy or autologous/allogeneic stem cell transplantation. This is a placebo-controlled study in which patients will receive study medication daily for 6 months, during which time the dose of study medication may be adjusted based upon individual platelet counts and bone marrow blast counts. All subjects will receive best standard of care (platelet transfusions, mild chemotherapy, cytokines, valproic acid, all-trans retinoic acid, ESAs or G-CSF) in addition to study medication. Subjects taking placebo may be allowed to crossover to eltrombopag treatment if a clinically and statistically significant improvement in bone marrow blast counts is seen in subjects treated with eltrombopag.
A double-blind, randomized, placebo-controlled phase I/II study to evaluate the safety and tolerability of eltrombopag olamine, a thrombopoietin receptor agonist, administered for 6 months as oral tablets once daily in adult subjects with advanced MDS, sAML/MDS, or de novo AML. Study medication may be increased up to 300 mg (150 mg maximum dose for East Asian subjects), based upon individual platelet counts and bone marrow blast counts.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
98
thrombopoietin receptor agonist
Placebo tablets with no active pharmaceutical ingredient
GSK Investigational Site
Birmingham, Alabama, United States
GSK Investigational Site
Santa Monica, California, United States
GSK Investigational Site
Stanford, California, United States
GSK Investigational Site
Coral Springs, Florida, United States
GSK Investigational Site
Lake Worth, Florida, United States
Safety and tolerability parameters including non-hematological laboratory Grade 3/Grade 4 toxicities, change in bone marrow blast counts from baseline and adverse events reporting.
Time frame: Approximately 46 months
Proportion of subjects with a baseline platelet count <20 Gi/L and an increase to >20 Gi/L and by at least 2x baseline; or a baseline platelet count between >=20-<30 Gi/L and an absolute platelet count increase to >=50 Gi/L at any time during treatment.
Time frame: Approx. 46 months
Frequency and number of units of platelet transfusions during the treatment and follow-up periods for eltrombopag- and placebo-treated subjects.
Time frame: approx 46 months
The incidence and severity of bleeding events, measured using the World Health Organization (WHO) Bleeding Scale, during the treatment and 4 week follow-up periods for eltrombopag- and placebo-treated subjects.
Time frame: approx. 46 months
Overall survival (OS) of eltrombopag- and placebo-treated subjects.
Time frame: approx. 46 months
Change in health-related quality of life as measured using the EQ-5D questionnaire.
Time frame: approx. 46 months
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GSK Investigational Site
Atlanta, Georgia, United States
GSK Investigational Site
Baltimore, Maryland, United States
GSK Investigational Site
Boston, Massachusetts, United States
GSK Investigational Site
Detroit, Michigan, United States
GSK Investigational Site
Kansas City, Missouri, United States
...and 55 more locations